Gastro-Esophageal Reflux Disease (GERD) is a common chronic disorder affecting millions of people both in the United States and worldwide. Its main symptoms, amongst others, are: heartburn, a burning sensation in the chest, occasionally a bitter taste in the mouth, cough, back pain etc.
Currently, GERD is treated with a class of drugs called proton pump inhibitors (PPI), such as, for example omeprazole and esomeprazole. Recent reports link PPI treatments as possible causes of stomach cancer, hip fracture and alkaline reflux. Additionally, PPI is not recommended for chronic patient use.
Food allergy (e.g., peanut allergy) is a growing public health concern in the United States and all over the world. Scientists are reporting an increase in food allergy over the past decade. In particular, peanut allergy among young children doubled between 1997 and 2002. Approximately 12 million Americans suffer from food allergy, with 6.9 million allergic to seafood and 3.3 million allergic to peanuts or tree nuts. It is estimated that between 150 and 200 people die annually from anaphylaxis to food; including children and young adults. Approximately 2.2 million school-aged children have food allergy. Food allergic reactions result in over 30,000 emergency room visits each year.
Food allergy is the leading cause of anaphylaxis (a severe allergic reaction) outside the hospital setting. Other causes of anaphylaxis include exercise, insect sting, latex, medication, and idiopathic reactions. Eight foods account for 90% of all reactions in the U.S.: milk, eggs, peanuts, tree nuts (walnuts, almonds, cashews, pistachios, pecans, etc.), wheat, soy, fish, and shellfish. There has been no cure for food allergy. Strict avoidance of the allergy-causing food is the only way to prevent a reaction. Food Allergy is also related to other Gastrointestinal conditions, such as increase of the intestinal permeability and GI irritation, Gastroesophagial Reflux Disease, IBD etc.
COPD (Chronic Obstructive Pulmonary Disease) is a pulmonary disease in which the lung is damaged, thus causing the patient difficulties in breathing. In COPD, the airways that carry air in and out of the lungs become partially blocked, and it becomes difficult to inhale and exhale. COPD is a major cause of death and illness throughout the world. It is the fourth leading cause of death in the U.S. and the world and causes serious, long-term disability. The number of people with COPD is currently on the rise. More than 12 million people are currently diagnosed with COPD and an additional 12 million are likely to have the disease and are undiagnosed. When COPD is severe, shortness of breath and other symptoms can get in the way of doing even the most basic tasks, such as performing light housework, taking a walk, even bathing and getting dressed. COPD develops slowly, and can worsen over time. Symptoms of COPD include constant coughing, shortness of breath, excess sputum production, feeling difficulty in breathing, inability to take a deep breath and wheezing. Currently, COPD is treated with Anticholinergic, Combination Inhaler, Corticosteroids, Inhaled Beta-2 Agonists, Inhaled Corticosteroids, Mucolytics, Oral Beta-2 Agonists and/or Theophyllines.
Anticholinergics:
Anticholinergics are used in the treatment COPD because they widen the airways by relaxing smooth muscle. They do this by blocking acetylcholine receptors. Acetylcholine is a chemical produced by the brain that causes muscle contraction, which in turn constricts airways. Anticholinergics are considered first-line therapy for COPD. The only inhaled anticholinergic agent available in the United States is ipratropium (Atrovent).
Combination Inhalers:
Recently, a new product called Advair was FDA approved for asthma but it may also be beneficial in the treatment of COPD. It combines two medications that have been on the market, salmeterol (a longer acting beta2-agonist) and fluticasone (a steroid). Many patients require both medications to help prevent asthma or COPD symptoms from worsening, but until now were only available as separate inhalers. Advair cannot be used to quickly relieve asthma or COPD symptoms, it is to be taken on a scheduled basis without regard for the symptoms the patient is having at that particular moment.
Another combination inhaler is Combivent. It contains two medications: albuterol and ipratropium. Albuterol is an inhaled beta-agonist that works in the lungs to open airways and allow for easier breathing. It does this by stimulating the beta-receptors, which are a certain type of receptor located in the lungs, which help regulate constriction and dilation of the airways. Ipratropium is an anticholinergic used in the treatment of COPD to widen the airways by relaxing and opening air passages to the lungs, making it easier to breathe.
Corticosteroids:
Corticosteroids are used to treat many health conditions. This drug class is mainly used for treating asthma, but it has been used for treating COPD. Oral corticosteroids decrease inflammation in the lungs that is associated with COPD. They may take longer to work than inhaled corticosteroids, since they have to travel through the bloodstream before they get to the lungs to work. Corticosteroids are only used in COPD patients who do not respond well to other standard therapies.
Inhaled Beta-2 Agonists:
Beta2-agonists work in a manner similar to adrenaline, opening airways and easing breathing. They work by binding with, and thus stimulating, “beta2-receptors” that line the cell walls of the lungs and the bronchioles. The effect of this stimulation is to relax smooth muscles and widen the airways. In COPD, beta2-agonists should be scheduled instead of taken on as needed basis. Possible side effects to the beta2-agonists include shakiness, rapid heartbeat, and upset stomach.
Until recently, all available beta2-agonists were ones that worked quickly but lasted for a relatively short time—about 4-6 hours. Longer-acting beta2-agonists have since been introduced. They cannot be used to quickly relieve symptoms, because there is a delay before they start working. Currently there are two on the market: salmeterol (Serevent) and formoterol (Foradil). Longer-acting beta2-agonists are prescribed as maintenance medications which are to be taken on a scheduled basis without regard for the symptoms the patient is having at that particular moment. A short-acting beta2-agonist is best to treat acute symptoms of shortness of breath.
Inhaled Corticosteroids:
Corticosteroids suppress the body's production of substances that trigger inflammation and reduce the production of substances that maintain inflammation. This drug class is mainly used for treating asthma, but it has been used for treating COPD. Corticosteroids are only used in COPD patients who do not respond well to other standard therapies.
Mucolytics:
This class of drugs is used to thin the mucus associated with cough caused by thick mucus. Mucolytics make it easier to clear the mucus, which can be irritating and cause a cough.
Oral Beta-2 Agonists:
Oral beta2-agonists works in a similar fashion to inhaled beta2-agonists, but they may take longer to work than the inhaled formulation. Oral beta-agonists must be absorbed in the digestive tract and travel through the circulatory system before they begin working in the lungs, whereas the inhaled formulations go straight to the lungs.
Theophyllines:
Theophyllines appear to widen airways by relaxing the smooth muscles surrounding the airways. Theophylline is also used as a long-acting bronchodilator to prevent COPD symptoms. Taken orally as tablets, capsules, or liquids, theophylline is available in immediate-release and controlled-release formulations as well as injection (aminophylline).
HDC Inhibitors:
7-Amino-4,5,6-triethoxy-3-(5,6,7,8-tetrahydro-4-methoxy-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-yl)phthalide or tritoqualine is a drug, currently formulated in 100 mg tablets and sold in pharmacies in Europe for the treatment of allergy.
Tritoqualine is an inhibitor of the enzyme histidine decarboxylase (HDC), which catalyzes histidine decarboxylation in vivo to produce histamine, an endogenous biogenic amine, plus carbon dioxide. Inhibiting histamine production in the body is proposed to ameliorate symptoms of allergy.
Leukotriene Receptor Antagonists:
Leukotriene Receptor Antagonists (LRAs), e.g., Montelukast and Zafirlukast) have been traditionally used for the treatment of asthma.
H1 Blockers and H2 Blockers:
H1 and H2 receptors are histamine receptors activated by endogenous histamine. H1 blockers (anti-H1) and H2 blockers (anti-H2) have shown some protection against gastrointestinal injury caused by the administration of Nonsteroidal Anti-inflammatory Drugs (NSAIDS). Accordingly, to avoid or alleviate this problem, NSAID compositions containing as protectants against gastrointestinal injury, an alkalizing agent together with H1 blockers, H2 blockers, beta-adrenergic agonists, or combinations thereof have been used (U.S. Pat. No. 5,071,842).
Despite the available treatments, additional and alternative therapies which are more effective to treat or prevent COPD and/or gastrointestinal conditions ameliorated by proper histamine management (e.g., GERD and/or food allergies) and pharmaceutical formulations for use in such therapies are needed.